CN1399565A - Propellant free spray-on skin patch composition for improving wound healing and for drug administration - Google Patents

Abstract

Propellant-free spray-on skin patch composition comprising at least one substantially water insoluble film forming agent, at least one film plasticiser agent, at least one water soluble compound, at least one organic solvent and optionally a physiologically active ingredient or pro-drug thereof. The composition forms a flexible, porous and physiologically compatible skin patch when sprayed onto skin and allowed to dry. Also described are methods of improving wound healing using the above composition to form a protective film over the wound, and a spray patch transdermal drug delivery system for delivering to or through the skin a physiologically active ingredient or a prodrug thereof.

Description

A kind of propellant free spray-on skin patch composition that is used to promote wound healing and administration

Invention field

The present invention relates to a kind of spray form skin patch composition of non-aerosol and use it to promote wound healing, and/or give the method for patient physiological active component.The invention still further relates to a kind of spray on skin patch drug delivery system.Other aspects of the present invention will be apparent from following explanation.

Background of invention

Though existing several skin patch compositions can be used for forming layer protecting film on the market on wound, there are some problems in they.Present known spray form skin patch adopts water-insoluble polymer to be dissolved in the form of organic solvent basically, has a kind of suitable propellant simultaneously its form with aerosol is used.A significant disadvantage of such compositions is, after using on the skin and becoming dry, can form the membrane structure of atresia, hinders gas and dampness to pass through.And the dampness of not removing the wound causes having gathered under the film surface too much dampness, causes the destruction and the possibility of infection of wound.

Same debatable is that owing to be to pass through the administration of aerosol mode under propellant helps, the spray form skin patch uses with very high pressure, can cause patient's pain or discomfort when being used for the affected part.Thought before and from such compositions, removed propellant that so that compositions can be impossible in administration under the lower pressure, reason was it has been generally acknowledged that the existence of propellant is necessary for the nozzle blockage that prevents the compositions ejection.

Also proved in the past and used known spray form skin patch composition can allow microorganism under film covers, grow, caused wound infection as noted above.

Tradition once used the medicine of simple non-occlusive to transport prevention or the treatment that system is used for local skin morbid state or situation.These medicines transport system and generally include volatility and/or non volatile media, and its Chinese medicine and media compositions are applied topically to skin, are directly used in to be tried around skin area or its.These medicines transport the form that system adopts Emulsion, cream, ointment, foam, gel, liquid, spray and aerosol usually.Such medicine transports system and generally is used for the treatment of scytitis, partial fungus and bacterial infection, soft tissue contusion, parasite and local anesthesia.The limitation that the medicine of this type transports system is, since multiple factor (may comprise that medication interval is short), general inapplicable this administration type of systemic administration.The subject matter of this area present situation relates to because medicine is low through skin dose, can not fully control the administration rate, or needs very large administered area, thereby lacks the effect of systemic administration.Medicine is that medicine is easy to be washed off to the problem of skin low penetration, or is stained with on medicated clothing and other surfaces.

The dermal drug of medicine transports system may represent one of the most ancient in history human administering mode.The human in early days skin injury that may use resin and Animal fat to treat wound and burn and cause.These materials remain unchanged to a great extent as the topical of active substance, up to this century.The notion of transdermal whole body administration is formally advocated by Dr Alejandro Zaffaroni at first, for example, from the seventies in 20th century in early days, in US patent 3598122 and 3731683, propose.But the administration of transdermal whole body provides a kind of effective ways that improve biological active substances biology availability, and with traditional route of administration, drug absorption is very poor, and/or oral dose toleration difference or impossible.

But transdermal formulations is limited.For example, how very slow through skin polar medicine is.Because most drug has polarity, this restriction is very serious, and the same fact is the stimulation that many medicines can cause the topical application position.

The common method of a known help medicine transdermal is the thermodynamic activity that increases medicine.The thermodynamic activity of medicine is to select proportional with its concentration and carrier.According to thermodynamic principles, the maximum activity of medicine is relevant with the activity of pure medicine crystal.

From the seventies in 20th century, the administration of transdermal whole body is mainly concentrated and is remained on the transdermal patch device.These patch devices are similar to binder, are attached to complete skin surface for a long time, distribute to reach the required whole body of medicine or other physiological agents.These transdermal patch devices sealing skins also make medicine and volatile matter and vehicle excipients are stayed between skin and the outer impervious notacoria.Notacoria prevents vehicle excipients, volatile matter and medicine evaporation or diffuses in the environment except that the particular skin target site.Often cause local skin to stimulate action time for making medicine and excipient transfer to prolongation required in the skin from patch.Stimulation is by medicine, volatile matter, vehicle excipients or is used for that the patch device is attached to the long-time and contact skin of binding agent on the skin and causes.The closing characteristics of patch device has also limited natural " breathing " ability of skin, and this can cause discomfort, and increases skin irritant risk.Add the problem of the complicated and expensive production method of transdermal patch device, be necessary to improve transdermal drug and transport system, make administration easy, preparation is simple and cost is low.

Use oversaturated system to produce unusual high thermodynamics electromotive force, can increase thermodynamic activity (Coldman, et al, the J.Pharm.Sci.58 (9): 119,1969) of medicine.But the major limitation that relies on oversaturated topical carrier is a formulation instability before skin uses and in the use.Thus, it is in non-closure volatility: non-volatile clinical value of transporting in the carrier is limited, because prescription is in case touch medicated clothing, medicine often forms precipitation; Thereby prescription is oversaturated no longer just, and any enhanced percutaneous absorbs and also stops immediately.

Other strengthen scholar such as the Kondo that transdermal drug transports with supersaturation, and et al (J.Pharmacobio-Dyn., 10:743,1987) once relied on and uses anti-nucleating polymer to make prescription stable.But the stable pharmaceutical formulation of using polymer forms a considerable surface mass on skin, and continues a plurality of hours but not stayed put in several minutes.So, although advocating, Kondo use a kind of quantized spraying to carry these prescriptions, in fact to obtain a kind ofly to use short and non-closure medicine that still keep clinical effective skin penetration rate to improve of time to transport system be impossible.

Therefore, the purpose of this invention is to provide a kind of spray form skin patch composition, overcome with prior art under compositions some problem relevant with system.Other purposes of the present invention will be apparent from following detailed.

Summary of the invention

According to one embodiment of the invention, a kind of non-aerosol spray shape skin patch composition is provided, it comprises:

(a) at least a water-insoluble basically film former;

(b) at least a film plasticizer;

(c) at least a water soluble compound; With

(d) at least a organic solvent;

When being sprayed onto on the skin and after drying, compositions forms a softness, the porous compatible skin patch of physiology simultaneously.

Compositions also can comprise physiologically active ingredient or its prodrug when being used for wound location.

According to another embodiment of the invention, a kind of non-aerosol spray shape skin patch composition is provided, it comprises:

(a) at least a water-insoluble basically film former;

(b) at least a film plasticizer;

(c) at least a water soluble compound;

(d) at least a organic solvent; With

(e) one or more physiologically active ingredients or a kind of its prodrug;

When being sprayed onto on the skin and after drying, compositions forms a softness, the porous compatible skin patch of physiology simultaneously, provides the transdermal of medicine to transport.

According to another aspect of the present invention, provide a kind of spray form patch transdermal drug to transport system, in containing the water-fast porous membrane structure of storage of pharmaceutical, comprised at least a physiologically active ingredient or its prodrug.

According to a further embodiment of the present invention, a kind of method that promotes wound healing or need the patient physiological active component of this treatment is provided, the method comprises the above-mentioned composition to patient's wound or dermal administration effective dose.

Others of the present invention are described below.The detailed description of invention

In entire description and claims subsequently, unless context requires different, word " comprises " will be understood that expression comprises a described integer or step, or one group of integer or step, but not except any other integer or step, or integer or step group.

Term " non-aerosol " is meant that compositions does not comprise the propellant that is used for transporting compositions under pressure.By way of example, compositions can be used so easily: utilize the air that pumps into from the dispense container of a pump group type, compositions is sprayed from nozzle under low relatively pressure.

The present invention has several aspects.One main aspect, skin patch composition is fit to be sprayed onto on the wound, for example incised wound, skin ulcer, abrade, burn or other illing skins.On the other hand, spray form patch skin transports compositions and is suitable for normal skin, transports or mode by skin (transdermal) gives the patient physiological active component as a kind of, as systemic active medicine or its prodrug.Under these circumstances, the spray form skin patch composition is preferably with quantized dosed administration.

Of the present invention one primary aspect, said composition comprises at least a water-insoluble basically film former, at least a film plasticizer, at least a water soluble compound and at least a organic solvent.These compositions should be that physiology is compatible certainly, when mix be used for skin and become dry after, compositions forms a softness, compatible porous skin patch or the skin cover film of physiology, and degrades as time passes.

The spendable film former of the present invention comprises acrylic acid and derivant thereof, polyacrylic acid and derivant thereof (as polybutyl methacrylate and polymethylacrylic acid), polymethyl acrylate, ascorbic palmitate, carbomer, Brazil wax, cellulose derivative is (as Cellacefate, rosca mellose sodium, hydroxyethyl-cellulose, hydroxypropyl cellulose, hydroxypropyl emthylcellulose, ethyl cellulose and related compound, hydroxypropyl O-phthalic acid methyl cellulose, hypromellose phthalate, crospovidone and derivant/related compound thereof), spermol and derivant thereof, microwax, poloxamer, Polyethylene Glycol, polyurethanes, polyvinyl acetate, poly-acetic acid O-phthalic vinyl acetate, polyvinyl alcohol, polyvinyl alcohol, ketopyrrolidine, silicone rubber and derivant thereof, lac, triglyceride derivative.These film former dissolve in organic solvent, as are dissolved in the organic solvent of the skin-compatible of using in dermatological, pharmacy and the veterinary.

Also may comprise some water-insoluble basically film former in the compositions, can form a softish skin patch when being used for skin equally when mixing.

Said composition should comprise at least a film plasticizer, be used for the thin polymer film that softening film former forms, enough soft to guarantee it, can not cause with skin one starting in use zone and break and strip off (at least during the expected service life of skin patch).The example of the film plasticizer that is fit to comprises that poly-butyl phthalate, benzyl benzoate, dibutyl sebacate, dimethyl phthalate, dibutyl phthalate, glycerol triacetate, ethylene glycol and derivant thereof, benzyl benzoate, glycerol, mineral oil, lanolin alcohol are (as C _1-8Alcohol), oil and lanolin alcohol, Polyethylene Glycol, glycerol, sorbitol, glycerol triacetate, triethyl citrate, propylene glycol, chlorobutanol, Oleum Ricini and gelatin.

An importance of the present invention is that the skin patch that forms with said composition is porous.This porous realization is by comprising at least a water soluble compound in compositions, being combined in the thin polymer film when being used for skin.The existence of water soluble compound does not limit enforcement of the present invention, thinks to cause that when thin film contacts with dampness this compound molecule leaches thin film, and its result forms fenestra in thin film.These holes allow gas and steam by the skin patch thin film.In a preferred version of the present invention, water soluble compound also has another effect in compositions, for example as physiologically active ingredient.The example of water miscible physiologically active ingredient comprises antibiotic quaternary ammonium compound, as Cetrimide, alkylaryl tri alkyl ammomium chloride, alkylaryl trimethyl ammonium chloride, bromine diamantane (obsolete) ammonium (amantanium bromide), benzalkonium chloride, benzethonium chloride, the bromobenzyl moon first ammonium, cetalkonium chloride, cethexonium bromide, hexadecyltrimethylammonium chloride and cetyldimethylethylambromide bromide ammonium.

Of this sort chemical compound can be combined in the thin film equably, directly acts on the antibacterial on the damaged skin zone that thin film covers, and stays a plurality of fenestras in film, make its down skin can breathe and perspire, prevent from simultaneously to grow anaerobe under the thin film.The unique advantage of quaternary ammonium compound such as Cetrimide (cetrimide) because it has the surface activity effect, can help thin film to be attached to and use on the skin.Quaternary ammonium compound such as Cetrimide can also help the softening clot that is in contact with it and keep its flexibility.This effect helps to prevent wound, incised wound or abrasion incrustation, therefore is beneficial to the performance of antibacterial effect.

Other examples that can introduce the water soluble compound of compositions help skin patch inner air vent formation are antifungal, as chlorobutanol, phenol, phenol derivatives (as resorcinol), salicylic acid, the trivial suffering of bifurcation pyridine, amorolfine, amphotericin, azole derivatives and related compound (bifonazole, Nitric acid butoconazole, 2-methyl-1-(p-chlorobenzyl)benzimidazole, clotrimazole, croconazole, econazole, enilconazole, fenticonazole, fluconazol, flutrimazole, isoconazole, itraconazole, ketoconazole, lanoconazole, miconazole, omoconazole, Saperconazole, Demlofix, sulconazole, terconazole (triaconazole), tioconazole), benzoyl disulphide, bromine chlorine water poplar anilide, buclosamide, Butenafine, sad candicidin, Chlorphenesin, ciclopirox olamine, cilofungin, D25, flucytosine, griseofulvin (criseofulvin), hachimycin, siccolam, hamycin, amidine at the bottom of the isethionic acid hydroxyl, loflucarban, mepartricin, pimaricin, furfural oxime, paranitrophenol, nystatin, pentamycin, propanoic acid, protiofate, pyrrolnitrin, Sulbentine, terbinafine, tolciclate, tineatonsurans is moved back, triacetin, undecylenic acid.Water soluble medicament is not limited to antimicrobial drug or antifungal agent.Also can use skin protectant such as ethoxylation lanoline, alcohols (as C ₄To C ₈Alcohol, for example methanol, ethanol, propanol or isopropyl alcohol) and glycerol.Also can use and anyly have good water solublity and in volatile organic solvent such as C4 to C8 alcohol (for example methanol, ethanol, propanol or isopropyl alcohol), acetone, ethyl acetate, dimethyl ether and other polar solvent mild or moderate dissolved substances.

In order to help this skin patch composition to use with spray pattern, compositions will comprise at least a organic solvent, preferred volatile organic solvent.As just for example, one can be selected from acetone, ethyl acetate and isopropyl alcohol to multiple solvent.Preferred these solvents are because they have certain bactericidal activity.Other adoptable solvents comprise: alcohols, for example C _1-10Alcohols is (as benzylalcohol, ethanol, methanol, butanols, isobutanol, diacetone alcohol), chlorinated hydrocabon is (as dichloromethane, carbon tetrachloride, trichloroethylene, trichloroethane (chlorothene SM)), esters is (as methyl acetate, ethyl acetate, propyl acetate, n-butyl acetate, isobutyl acetate, pentyl acetate, the own ester of 2-guanidine-acetic acid, duPont DBE, Exxate 500,700,900), ethylene glycol and ether/ester derivant, 1,2 ethylene glycol, phenylmercuric acetate (PM acetate), ethylene glycol monobutyl ether, Carbritol acetic acid, the Carbritol butyl acetate, Ektapro EEP, hydro carbons is (as toluene, Eyxlene, VM﹠amp; The P Petroleum, solvent naphtha, aromatic 100, aromatic 150), ketone is (as acetone, methyl. ethyl ketone, methyl butyl ketone), ethers (as dimethyl ether), benzyl benzoate, isopropyl myristate, acetonitrile, ethyl oleate, glycerol, glycofurol (tetraethylene glycol (TEG)), propylene glycol, Polyethylene Glycol (PEG), hexane, normal hexane, glycol ether, dichloromethane, chloromethane, octyl dodecanol, toluene, trichloroethane, diethyl phthalate and dibutyl phthalate.These solvents are volatile, and the use amount in dermatological preparation does not produce substantive the stimulation to skin usually, promptly is that pharmacy is acceptable.Solvent volatilizees rapidly after being administered on the skin.Wherein may comprise a small amount of non-volatile solvents (2%v/v that for example, is less than cumulative volume).

The spray form skin patch composition that is applied to treat wound can be chosen wantonly and comprise one or more physiologically active ingredient, or its prodrug, for example can be following one or more compositions or its combination: fastoperation antibacterial (as the bromine alkanamine), long effect antibacterial be (as triclosan, benzyl benzoate, dibutyl sebacate, dimethyl phthalate, dibutyl phthalate, triacetin, glycol and derivant thereof, corticosteroid, analgesics, the chemical compound with anti-inflammatory activity, antihistaminic and biologically active peptide or biological activity protein.Listed activating agent and the unrestricted characteristic that can introduce the physiologically active ingredient of said composition are because any and other components compositions are compatible and can all think to belong to this category by being ejected on the skin effectively the medicament of administration.The detailed physiologically active ingredient that can be used for this respect was described when spray form patch dermal drug of the present invention transports Composition Aspects in following relating to.

Used term " fastoperation " and " long effect " antibacterial be that the short effect of imagination antibacterial can produce the antibacterial activity effect about one to four hour in site of administration, and long effect antibacterial can show that activity reaches about four hours to about 48 hours.Available this area conventional method is measured antibacterial activity, comprise from wound location and get a swab, monitoring be exposed to the propagation and the vigor of microorganism behind the antibacterial of surveying.

When the water-soluble component in the said composition was a kind of physiologically active ingredient, one or more optional physiologically active ingredient can be identical or different.

According to another aspect of the present invention, provide a kind of spray form patch dermal drug to transport compositions, it comprises:

(a) at least a water-insoluble basically film former;

(b) at least a film plasticizer;

(c) at least a water soluble compound;

(d) at least a organic solvent; With

(e) one or more physiologically active ingredients or a kind of its prodrug;

When being sprayed onto on the skin and after drying, compositions forms a softness, the porous compatible skin patch of physiology simultaneously, provides the transdermal of medicine to transport.

Physiological agents or its prodrug comprise anyly having part or whole body active agents as used herein, and compatible with porous membrane of the present invention.These medicaments can transport by the skin transdermal, need not transdermal enhancer (it may cause skin irritation or allergy).The example of physiologically active ingredient or its prodrug comprises, one or more following compositions by the convenient classification of treatment type.

Digestive system

Diarrhea such as diphenoxylate, loperamide and hyoscyamine.

Cardiovascular system

Antihypertensive such as Aiselazine, minoxidil, captopril, enalapril, clonidine, prazosin, debrisoquine, diazoxide, guanethidine, methyldopa, reserpine, arfonad.

Calcium channel blocker such as diltiazem, Felodipine, amlodipine, nitrendipine, nifedipine and verapamil.

Anti-arrhythmic such as amiodarone, flecainide, disopyramide, procainamide, mexiletine and quinidine.

Anti-anginal drug such as nitroglycerin, Eritrityl Tetranitrate, nitropenthrite, mannitol hexnitrate, Perhexiline, sorbide nitrate and nicorandil.

B-adrenergic receptor blocker such as alprenolol, atenolol, betadrenol, carteolol, labetalol, metoprolol, nadolol, nadoxolol, oxprenolol, pindolol, Propranolol, sotalol, timolol and timolol maleate.

Cardiac glycoside such as digoxin and other cardiac glycosidees and bitter edible plant alkali derivant.

2-adrenergic agonist components such as epinephrine, norepinephrine, fenoterol, isoproterenol, orciprenaline, rimiterol, albuterol, salmaterol, terbutaline, dobutamine (dobutambe), phenylephrine, phenylpropanolamine, pseudoephedrine and dopamine.Vasodilator such as cyclandelate, isoxsuprine, papaverine, dipyridamole, sorbide nitrate, phentolamine, nicotinyl alcohol, co-dergocrine, nicotinic acid, nitroglycerin, nitropenthrite and Landrina.

Migraine preparation such as Ergotamine (ergotamine), dihydroergotamine, methysergide, pizotifen and sumatriptan.

Influence the medicine of blood and hemopoietic tissue

Anticoagulant medicine and thrombolytic agent such as warfarin, dicoumarol, Low molecular heparin (as Enoxaparin); Plasminogen activator such as streptokinase and reactive derivative thereof, t-pA and derivant thereof and similar medicine.

Hemorrhage such as aprotinin, tranexamic acid and protamine.

The central nervous system

Antipyretic analgesic comprises opium kind analgesics, as buprenorphine, dextromoramide, dextropropoxyphene, fentanyl, Ah ,'s sufentanil, hydromorphone, methadone, morphine, oxycodone, papaveretum, pentazocine, Pethidine, phenoperidine, codeine and dihydrocodeine.Other comprise aspirin (aspirin), acetaminophen and phenazone.

Hypnotic and sedative such as barbiturates, amobarbital, butobarbital and pentobarbital and other hypnotic and sedatives such as chloral hydrate, clomethiazole, hydroxyzine and meprobamate.

Antianxiety drugs such as Benzodiazepines, alprazolam, bromazepam, chlordiazepoxide, clobazam, chlorazepate, diazepam, flunitrazepam, flurazepam, lorazepam, nitrazepam, oxazepam, temazepam and triazolam.

Tranquilizer and psychosis such as phenothiazines (as chlorpromazine, fluphenazine, periciazine, perphenazine, promazine, Thiopropazate, thioridazine and trifluoperazine), butyrophenones, droperidol, haloperidol and other psychosis such as pimozide, tiotixene and lithium.

Antidepressants such as tricyclic antidepressants (amitriptyline, clomipramine, desipramine, dosulepin, imipramine, nortriptyline, opipramol, sieve difficult to understand are for woods and trimeprimine), Fourth Ring class antidepressants (as mianserin), oxidase inhibitor (as isocarboxazid, phenelzine, tranylcypromine and moclobemide) and selectivity 5-hydroxy tryptamine reuptake inhibitor (as fluoxetine, paroxetine, citalopram, fluvoxamine and Sertraline).

Central nervous system stimulant such as caffeine.

Anti-presenile dementia medicine such as tacrine.

Antiparkinsonian drug such as amantadine, benserazide, carbidopa, levodopa, benzatropine, biperiden, benzhexol, procyclidine and dopamine-2 antagonisies are (as S (-)-2-(N-propyl group-N-2-thiophene ethylamino)-5-hydroxy tetrahydro naphthalene (N-0923).

Antuepileptic such as phenytoin, valproic acid, primidone, phenobarbital, mebaral and carbamazepine, ethosuximide, first, phensuximide, sultiame and clonazepam.

Bendectin, antinauseant such as phenothiazines (prochlorperazine, thiethylperazine) and 5-hydroxy tryptamine-3 receptor antagonist (as ondansetron and granisetron) and other are as dimenhydrinate, diphenhydramine, metoclopramide, domperidone, scopolamine, hydrobromic acid, Scopolamine Hydrochloride, clebopride and brompride.

Musculoskeletal system

Nonsteroidal antiinflammatory drug comprises its available racemic mixture or each enantiomer, as ibuprofen, flurbiprofen, ketoprofen, alclofenac, diclofenac, aloxiprin, aproxen, aspirin, diflunisal, fenoprofen, indomethacin, mefenamic acid, naproxen, Phenylbutazone, piroxicam, salicylamide, salicylic acid, sulindac, deoxidation sulindac, tenoxicam, tramadol and ketorolac.

Can comprise salicylamide with the nonsteroidal antiinflammatory drug that transdermal enhancer is united prescription in addition, salicylic acid, flufenisal, salsalate, triethanolamine salicylate, aminophenazone, phenazone, oxyphenbutazone, azapropazone, cinnopentazone, flufenamic acid, Sai Li, clonixin, meclofenamic acid, flunixin, colchicine, Demecolcine, allopurinol, oxipurinol, benzydamine hydrochloride, the dimefadane, indoxole, intrazole, the hydrochloric acid mimbane, the hydrochloric acid paranyline, tetridamine, the hydrochloric acid benzindopyrine, fluprofen, ibufenac, naproxol, fenbufen, cinchophen, diflumidone sodium, fenamole, flutiazin, metazamide, letimde hydrochloride, Nexeridine Hydrochloride, octazamide, molinazone, neocinchophen, nimazone, the citric acid proxazole, tesicam, tesimide, tolmetin and triflumidate (triflumidale).

Antirheumatic such as penicillamine, aurothioglucose, sodium aurothiomalate, methotrexate and auranofin.

Muscle relaxant such as baclofen, diazepam, cyclobenzaprine hydrochloride, dantrolene, methocarbamol, orphenadrine and quinine.

Medicament that uses in gout and the hyperuricemia such as allopurinol, colchicine, probenecid and sulfinpyrazone.

Hormone and steroid

Estrogen such as estradiol, estriol, estrone, ethinylestradiol, mestranol, diethylstilbestrol, dienestrol, epiestriol, estropipate and zeranol.

Progesterone and other progestogenss such as allylestrenol, dydrogesterone, lynestrenol, norgestrel, Norethynodrel,, norethindrone acetate, gestodene, levonorgestrel, medroxyprogesterone and megestrol.

Androgen antagonistic such as cyproterone acetate and danazol.

Estrogen antagonistic such as tamoxifen and epitiostanol and aromatase inhibitor (exemestane and 4-hydroxyl-androstenediol (androstenedione) and derivant thereof).

Androgens and anabolic hormones such as testosterone, methyltestosterone, clostebol acetate, drostanolone, furazabol, nandrolone, oxandrolone, stanozolol, acetic acid trenbolone, dihydrotestosterone, 17-Alpha-Methyl-nandrolone and fluoxymesterone.

5-alpha reductase inhibitor such as finasteride, turosteride, LY-191704 and MK-306.

Adrenocortical hormones such as betamethasone, betamethasone valerate, cortisone, dexamethasone, dexamethasone phosphate, fludrocortisone, flumetasone, fluocinolone acetonide, (fluocinonide desonide), fluocinolone acetonide, the fluorine chloronaphthalene gets, fluocortolone, Ha Xinaide, halopredone, hydrocortisone, 17-valeric acid hydrocortisone, the 17-hydrocortisone butyrate, the 21-hydrocortisone acetate, methylprednisolone, prednisolone, Prednisolone phosphate, prednisone, triamcinolone, the triamcinolone acetonide.

Can be used in addition promptly comprising cortodoxone with the example of the steroidal anti-inflammatory medicine of compositions, fluoracetonide, fludrocortisone, difluorsone diacetate, flurandrenolide, medrysone, amcinafal, amcinafide, betamethasone and ester thereof, chloroprednisone, clocortolone, descinolone, how ground gets, dichlorisone, difluprednate, the flucloronide, aniprime, flunisolide (flumsolide), flucortolone, the acetone flurandrenolide that contracts, fluperolone, fluprednisolone, meprednisone, the methyl methylprednisolone, 6.alpha.-fluoro-16.alpha.-methylprednisolone, cortisone acetate, the hydrocortisone cipionate, cortodoxone, flucetonide, fludrocortisone acetate, flurandrenolide, medrysone, amcinafal, amcinafide, betamethasone, betamethasone benzoate, chloroprednisone acetate, the acetic acid clocortolone, the descinolone acetonide, desoximetasone, the astroderm, difluprednate, the flucloronide, flumethasone pivalate, flunisolide acetate, fluperolone acetate, fluprednisolone valerate, alondra, prednisolamate, W-4869, triamcinolone hexacetonide, cortivazol, fluderma and nivacortol.Pituitary hormone and reactive derivative thereof or analog such as thyroliberin, thyrotropin, follicle stimulating hormone (FSH), metakentrin (LH) and gonadotropin releasing hormone (GnRH).

Blood sugar lowering such as insulin, chlorine sulphur third relaxes, glibenclamide, gliclazide, glipizide, tolazamide, tolbutamide and metformin.

Thyroxin such as calcitonin, thyroxine and liothyronine and antithyroid medicament such as carbimazole and propylthiouracil.

Other various hormone agents such as octreotides.

Pituitary inhibitors such as Ergolactin.

Ovulation induction agent such as clomifene.

Genitourinary system

Diuretic such as thiazide, relevant diuretic and button loop diuretic (bendroflumethiazide, chlorothiazide, chlortalidone, dopamine, cyclopenthiazide, hydrochlorothiazide, indapamide, mefruside, methyclothiazide, metolazone, quinethazone, bumetanide, etacrynic acid and furosemide) and isokalaemic diuretic (spironolactone, amiloride and triamterene).

Antidiuretic such as Desmopressin, lypressin and vassopressin comprise its reactive derivative or analog.

Medicament such as ergometrine, oxytocin and the gemeprost of obstetric drugs as acting on the uterus.

Prostaglandin such as Alprostadil (PGE1), prostacyclin (PGI2), dinoprost (prostaglandin F2-α) and misoprostol.

Antimicrobial drug

Antimicrobial drug comprises cephalosporins, as cefalexin, cefoxitin and cefalotin.Penicillins adds clavulanic acid, ampicillin, bacampicillin, benzathine benzylpenicillin, penicillin, carbenicillin, cloxacillin, methicillinum, phenethicillin, penicillin V, flucloxacillin, mezlocillin, piperacillin, ticarcillin and azlocillin as amoxicillin, amoxicillin.Tetracyclines is as minocycline, chlortetracycline, tetracycline, demeclocycline, doxycycline, metacycline and oxytetracycline and other tetracycline antibiotics.

Aminoglycoside such as amikacin, gentamycin, kanamycin, neomycin, netilmicin and tobramycin.

Antifungal agent such as amorolfine, isoconazole, clotrimazole, econazole, miconazole, nystatin, terbinafine, bifonazole, amphotericin, griseofulvin, ketoconazole, fluconazol and flucytosine, salicylic acid, fezatione, ticlatone, tolnaftate, triacetin, zinc, pyrrole sulfur father-in-law and pyrithione sodium.Quinolones such as nalidixan, cinoxacin, ciprofloxacin, enoxacin and norfloxacin.Sulfonamides such as phthalylsulfamethizole, sulfadiazine, sulfamethizole and sulfamethoxazole.

Sulfone class such as dapsone.

Other various antibiotic such as chloromycetin, clindamycin, erythromycin, erythromycin ethycarbonate, erythromycin propionate lauryl sulfate, erythromycin gluceptate, erythromycin ethylsuccinate, erythromycin lactobionate, Roxithromycin, lincomycin, natamycin, nitrofurantoin, spectinomycin, vancomycin, aztreonam, polymyxin IV, metronidazole, tinidazole, fusidic acid and trimethoprim; 2-thiopyridine N-oxide; Halogen compounds, particularly iodine and iodine compound are as iodo-PVP complex and diiodohydroxyquinoline (Iodoquinol); Hexachlorophene; Chlorhexidine; The chloramination compound; Benzoyl peroxide.

Antitubercular agent such as ethambutol, isoniazid, pyrazinamide, rifampicin and clofazimine.

Antimalarial such as primaquine, pyrimethamine, chloroquine, oxychloroquine, quinine, mefloquine and halofantrine.

Antiviral agents such as acyclovir and acyclovir prodrug, famciclovir, neat Fu Duoding, didanosine, stavudine, lamivudine, zalcitabine, Saquinavir, indinavir, ritonavir, n-docosanol, tromantadine and idoxuridine.

Vermifuge such as mebendazole, thiabendazole, niclosamide, praziquantel, Pyrantel Pamoate and diethylcarbamazine.

Cell toxicity medicament is as plicamycin, cyclophosphamide, dacarbazine, fluorouracil and prodrug thereof (as describing in international journal of Practical Pharmacy (International Journal of Pharmaceutics) 111:223-233 (1994)), methotrexate, procarbazine, 6-mercaptopurine and mucophenolic acid.

Antiseptic

Other available antimicrobial drugs or antiseptic comprise alcohols (as ethanol, isopropyl alcohol and methylated spirit); Anion surfactant (as quaternary ammonium compound, Benzalkonii Chloridum, western bent bromo-amine, cetylpyridinium chloride, bisdequalinium diacetate and dequalinium chloride)); Bisbiguanides (as chlorhexidine and salt thereof, as chlorhexidine diacetate and polymeric biguanides, as PMMB); Chlorine or chloride dose (as chloramines, sodium dichloro cyanurate and sodium hypochlorite); Dyestuff (as the bifurcation piperidine derivatives, viride nitens, crystal violet, magenta and peacock green); Iodophors (as povidone iodine); Mercurial (as chiomersal and mercurochrome); Oxidant (as hydrogen peroxide, peracetic acid and potassium permanganate); Phenoxyethanol; Phenethanol; And phenols (as chlorocresol, chloroxylenol, cresol, chlorophenol (triclosan), hexachlorophene and phenol).

Metabolism

Anoretics and weight reduction agent comprise dexfenfluramine, fenfluramine, amfepramone, Mazindol and phentermine.

The medicament of using in hypercalcemia is as calcitriol, dihydrotachysterol and reactive derivative thereof or analog.

Respiratory system

Cough medicine is as ethylmorphine, dextromethorphan and pholcodine.

Expectorant is as acetylcysteine, bromhexine, emetine, guaifenesin, hippo and saponin.

Decongestant is as phenylephrine, phenylpropanolamine and pseudoephedrine.

Bronchial spasmolytic agent is that woods, rimiterol, albuterol, sodium cromoglicate, cromoglicic acid and prodrug thereof (as describing in international journal of Practical Pharmacy (InternationalJournal of Pharmaceutics) 7:63-75 (1980)), terbutaline, ipratropium bromide, salmaterol and theophylline and theophylline derivant as ephedrine, fenoterol, Austria.

Allergy and immune system

Antihistaminic such as meclizine, cyclizine, chlorcyclizine, hydroxyzine, brompheniramine, chlorphenamine, clemastine, Cyproheptadine, dexchlorpheniramine, diphenhydramine, diphenylamine, doxylamine, mebhydrolin, pyrilamine, pheniramine, triprolidine, azatadine, diphenylpyraline, methdilazine, terfenadine, astemizole, loratadine and cetirizine.

Local anaesthetics such as bupivacaine, tetracaine, lignocaine, cinchocaine, cinchocaine, mepivacaine, prilocaine and etidocaine.

Horny layer lipid such as ceramide, cholesterol and free fatty are to promote reparation (Man, et al, dermatological studies magazine (J.Invest.Dermatol., 106 (5): 1096,1996) of skin barrier.

Neuromuscular blocking agent such as succinylcholine, A Ku ammonium, PANCURONIUM, atracurium besilate, dagger-axe draw ammonium, tubocurarine and Vecuronium.

Smoking cessation agent such as nicotine, amfebutamone and ibogaine.

Be fit to insecticide and other insecticides that part or whole body use.

The dermatological medicament, as vitamin A and E, acetic acid and tocopherol sorbate.

The anaphylactogen such as the house dust mite allergen of desensitization usefulness.

Nutrient, as vitamin, essential amino acids and essential fat.

Keratolytic agent such as alpha-hydroxy acid, hydroxyacetic acid and salicylic acid.

Psychicenergisers is as 3-(2-aminopropyl) indole, 3-(the amino butyl of 2-) indole and analog.

Anti-acne agents is as containing isotretinoin, tretinoin and benzoyl peroxide.

Antipsoriatic is as containing etretinate, cyclosporin A and calcipotriol.

Antipruritic such as capsaicin and derivant thereof such as vanillylnonanamide (Tsai, et al, Drug.Dev.Ind.Pharm., 20 (4): 719, (1994)).

Anticholinergic agent effectively suppresses the oxter perspiration and controls scorching hot.Following medicine tool anti-hidropoiesis, as methatropine nitrate, probanthine, scopolamine, methscopolamine bromide and the new gentle antiperspirant of a class, quaternary acyloxymethyl ammonium salts is (as by Bodor et al, at J.Med.Chem., describe among the 23:474 (1980), and in the United Kingdom specification No 2010270 that published on June 27th, 1979, describe).

Other physiologically active peptides and physiologically active protein, little peptide to middle molecular size, for example, vassopressin and human growth hormone.

Physiologically active ingredient or its prodrug be preferably dissolving in the concentration that medicine transports system, but come out to form medicine store in perforated membrane precipitable after the solvent evaporation.

What do not wish bound by theory is, Concentraton gradient is considered to the mode that biological agent or its prodrug adopt by skin.Think that the porosity characteristic of the patch that forms or thin film provides the effect of similar storage, makes some sites have the bioactive agent of high concentration on skin.Therefore the Concentraton gradient that forms is considered to order about medicament by skin, transports and produce the medicine that continues.Also it is believed that the porosity characteristic of thin film, gas and steam are passed through, and avoid being used for the relevant skin irritation problem of skin with transdermal films/patch.

But the depolymerization after after a while that is it of an advantage of the present composition, and unnecessary thin film is peeled off or cleaned.The time length of depolymerization is by adding blocking-up degree decision in the thin film that water soluble compound causes in the selection of film former and the compositions.By to these components selection, can change the service life of skin patch along with a design feature of compositions.For example, patch can such as depolymerization in 24 hours or 48 hours.

In another aspect of the present invention, provide a kind of spray form patch transdermal drug to transport system, contain in the water-fast porous membrane structure that medicine stores a kind of, comprise at least a physiological agents or its prodrug.

This medicine transports system and is fit to physiological agents by animal, comprises the transportation of people's skin surface or mucosa.This device toxicity is low, and is good especially at the toleration of animal skin surfaces or mucosa.

The present invention also provides a kind of and gives the medication of physiological agents or its prodrug of at least a whole body or local action to animal, and it comprises the physiological agents that the form of transporting system with compositions according to the present invention or medicine is used effective dose.

Preferred animal is behaved, but the present invention also extends to non-human animal's treatment, as animal (for example, Canis familiaris L. and cat), domestic animal together, and for example milch cow/beef cattle, sheep, horse, goat, pig and similar animal, and birds.

Surprisingly, compositions of the present invention and device promote activating agent or its prodrug by the absorption of skin and mucosa, have avoided significant medicine detrimental effect and toxicity in the art methods simultaneously.

The compositions of various aspects and medicine transport system according to the present invention, can introduce the mixture of a kind of medicine compounding ingredient, cosolvent, surfactant, emulsifying agent, antioxidant, antiseptic, stabilizing agent, diluent or two or more described components, to be fit to specific route of administration and dosage form.The amount and the type of the component of using should be compatible with structured polymer film.Can use a kind of cosolvent or other standard adjuvant, as surfactant, so that physiological agents or its prodrug keep desired concn at solution or suspension.

The medicine compounding ingredient can comprise paraffin oil, esters (as isopropyl myristic acid ester), ethanol, silicone oil and vegetable oil, preferably uses in greater than 1% scope.Surfactant such as ethoxylized fatty alcohol, glyceryl monostearate, phosphoric acid ester, with other emulsifying agents commonly used, surfactant preferably uses in 0.1% to 1% scope, and be used for the antiseptic such as the hydroxybenzoate of the preservation of chemical compound, preferably use with 0.01% to 0.5% amount.Typical cosolvent and adjuvant can be ethanol, isopropyl alcohol, acetone, dimethyl ether and gylcol ether (as carbitol), and amount that can 1% to 90% is used.

When using the mixture of a kind of medicine compounding ingredient, cosolvent, surfactant, emulsifying agent, antioxidant, antiseptic, stabilizing agent, diluent or two or more described components, these components must be compatible with the ability that becomes dry after the system applies.

Can use easily in a kind of mode that quantizes the dosage manual pump that just replacing according to non-aerosol spray shape skin patch composition of the present invention, preferably have a kind of locking device, can enter in the jar by occluded air.The organic solvent that comprises in the compositions is used to clean the nozzle of spraying, and prevents to play thin polymer film in the nozzle inner accumulated.Quantize dosing pump by using, make the thin film that sprays an accurate amount to skin, become possibility, and the concentration knowledge of physiologically active ingredient in the group of contacts compound, the administered dose that can guarantee active component is in strictness control.Its dependent variable that needs to consider in control delivery of active ingredients (especially when the non-quantized situation of using dosage) comprises the skin area that contacts compositions and the time span of contact skin.Certainly, a medical practitioner is easy to the effective dose that definite physiologically active ingredient need be used, and changes above-mentioned variable, to guarantee correct use amount.For the conspicuous factor of medical practitioner,, when the correct dose of determining for a particular patient, also need to consider as related patient's height, body weight, age, sex and general health situation.For example, dosage range can comprise active component in the scope of 0.01ng to 500mg, and as 0.01mg to 100mg, for example 0.1mg to 75mg or 1mg to 300mg are every dose.

According to various aspects of the present invention, the ratio of component includes, but not limited to 1% to 50%w/w film former, 0.1% to 20%w/w film plasticizer, 0.1% to 10%w/w water soluble compound and 30% to 90%w/w organic solvent.

In one embodiment, dermal drug transports compositions can comprise a kind of non-aerosol spray shape skin patch composition, and it comprises:

0.01% to 10%w/w one or more water soluble compounds

0.01% to 10%w/w one or more physiologically active ingredients

1% to 50%w/w polymethylacrylic acid

0.1% to 20%w/w poly-butyl phthalate

0% to 90%w/w isopropyl alcohol

0% to 90%w/w acetone

Ethyl acetate adds to 100%w/w,

When being ejected on the skin and after drying, compositions forms a softness, the porous compatible skin patch of physiology simultaneously.

Other physiology acceptable carriers, diluent, solvent or excipient also can be included in the compositions, as being widely known by the people in the medicine formulation art.The details of these materials is in MaxRemington ' s Pharmaceutical Sciences, 17 ^ThEdition, Mack PublishingCo, Easton Pennsylvania provides in USA one book, and its disclosure intactly is included in this as a reference.

Compositions according to the present invention can be used for Therapeutic Method, as, in healing behind treatment skin wound, fungal infection, the plastic operation, eczema, the skin or skin surface bacterial infection, athlete foot, the skin ulcer relevant with wound, burn, scald, sting, local anesthesia, pruritus, pain and other are aspect the method for this narration.

Zhi Liao pain can be rheumatalgia (as joint and myalgia), the pain relevant with skin ulcer, pain and similar this type of pain relevant with anal fissure herein.

Medicine-feeding part can be wound or disease position, or away from the affected part.

Other aspects of the present invention will be explained in the following non-limiting Examples.

Embodiment

Embodiment 1

Compositions is prepared as follows:

A kind of non-aerosol spray shape skin patch composition, it comprises:

0.05％w/w?centrimide

The 0.07%w/w triclosan

The 0.6%w/w chlorobutanol

The 10%w/w polymethylacrylic acid

1.2%w/w gathers butyl phthalate

The 4%w/w isopropyl alcohol

24%w/w acetone

Ethyl acetate adds to 100%w/w

Embodiment 2

The lasting release of antimicrobial acivity composition in the embodiment 1 set of applications compound

Sample

Receive contain in the Nalgene bottle according to one liter of the compositions of embodiment 1 preparation, verify.Bottle is labeled as " Ref.BX258 "

Method

Process is based on Australian Standard AS1157.1 and .2, and 1998, be introduced in BP and preserve the microorganism of stipulating in the efficiency assay.

With 1mL sample wetting film pad.After having done, the film pad is placed agar plate surface, contain the lawn culture of following microorganism on the agar plate.

Substrate Microorganism Attack quantity/flat board

^*TSA escherichia coli 3 * 10 ⁸

TSA staphylococcus aureus 3 * 10 ⁸

^*SDA Candida albicans 3 * 10 ⁶

SDA black aspergillosis (spore) 1 * 10 ⁷( ^*TSA=tryptone soy agar, the husky Borrow's agar glucose of SDA=) positive that be arranged in parallel and negative control.The dull and stereotyped 37 ℃ of incubations of TSA 3 days, the dull and stereotyped 25 ℃ of incubations of SDA 5 days. The result

Obvious growth is arranged on the G=pad

There is not obviously growth on the NG=pad

Behind the incubation, observe and dull and stereotypedly to go up, on the pad and the growing state under filling up, measure any inhibition zone.

Pad G or NG/

Microorganism The inhibition zone

Escherichia coli: NG/0.5mm

Staphylococcus aureus NG/0.5mm

Candida albicans NG/0.6mm

Aspergillus niger NG/ unrestraint district

Find

1. all have been stoped microorganism in the growth that contacts with product on the agar by the surface that Medico spray form binder covers.This and microorganism are irrelevant, no matter are

(a) escherichia coli, a kind of gram negative bacilli

(b) staphylococcus aureus, a kind of gram-positive cocci

(c) Candida albicans, a kind of pathogenic yeast

(d) Aspergillus niger, a kind of product spore mycete

2. the inhibition zone occurs when attacking (a) to (c), although this effect is not to be considered as necessity to product; Be that the spray form binder only needs to suppress growth in the spray area that covers open wound.Is not rely on product functionality to use at damaged skin with the usefulness of exterior domain.

3. contrast is consistent with expected results, that is, bacterial growth is not suppressed.

Embodiment 3

The effect of embodiment 1 compositions to dampening

This embodiment shows that embodiment 1 compositions is transparent, antimicrobial, waterproof, " spray form binder " that can wash, is applied to incised wound, minor cut or wound and scratch.Study its effectiveness in the artificial contusion of rabbit.Obtained following result:

1. testDate

On July 23,13 days to 1999 June in 1999

2. test material and method of testing

1) test animal: rabbit

2) test composition: embodiment 1 compositions

3) make 2 people's industrial injury mouths in rabbit back of the body central authorities

After contusion, observe treatment and non-treatment animal.

A) operational approach of manufacture of intraocular wound

Shave off the hair of rabbit back central authorities, cause 3cm with sand paper strong friction skin then ²Intrusion.

B) observe

Perform the operation and did macroscopic observation in back first day, second day, the 5th day and the tenth day respectively.At the tenth day rabbit is put to death, to check pathological tissue.

3. result

1) Visible observation

The visible change of operative site is as shown in following table 1:

Table 1

	Observation item	First day	Second day	The 5th day	The tenth day
						With embodiment 1 treatment	Area (the cm of operative site 2)	????3	??3	??3	??3
Congested	????-	??-	??-	??-
					Incrustation		????-	??-	??-	??-
Loose	????+	??-	??-	??-
					There is not treatment		Area (the cm of operative site 2)	????1.7	??1.7	??1.3	??1.0
Congested	????-	????-	??-	??-
						Incrustation	????+	????+	??+	??+
Loose	????-	????+	??++	??+++

2) inspection of operative site pathological tissue

Histopathologic analysis is as shown in table 2

Table 2

	With embodiment 1 treatment	Treatment target not
			Epidermis nipple papillary layer crust forms cellular infiltration	Normal normal no little	Thicken to extend to thicken and exist greatly

4. conclusion

1) incrustation in first day after surgery of Visible observation, untreated wound in the compressing of the visible surrounding tissue of operative site, and continues loose.

On the other hand, for the wound with embodiment 1 treatment, because the effect of compositions, we do not observe any atrophy of operative site.

2) histopathologic analysis of not treating wound is presented at operative site and is chronic dermatitis, and epidermis thickens, and papillary layer thickens and cellular infiltration.

On the contrary, with regard to regard to the specimen of embodiment 1 treatment, except slight cellular infiltration, do not observe significant abnormal.

Observe the general protection of therapeutic combination, and make normal structure regeneration wound.

The scratch of plastic operation tissue can be treated with said composition.Other application examples comprise the binder that cattle and other animal wounds are used.

Result of the test shows that compositions promotes the rapid healing of galled spots and surgical wound.

Embodiment 1 set of applications compound shows as a kind of real pseudo-skin effectively, and makes propagation under the rapid film of epithelium layer.By this method, dampen surface re-epithelialization rapidly, make epithelial cell hypertrophy and contraction be reduced to minimum simultaneously.

Embodiment 4

A kind of semi permeability wound spraying, embodiment 1 binder is used for Canis familiaris L. and cat

Embodiment 1 spraying has been used for the treatment of wound, dermatitis (eczema madidans), abscess, furunculosis, external otitis and postoperative wound.Before with embodiment 1 combination treatment, from different disease samplings originally, on the experimental determination antibacterial.

With forming behind skin patch or binder embodiment 1 combination treatment 3 days, estimate color and luster, sensitivity, humidity and the pus of area for treatment, and hydrophobicity, viscosity and squama produce.

93 animals (80 Canis familiaris L.s and 13 cats) are with the treatment of embodiment 1 binder.

Goal in research is for determining:

May 1) embodiment 1 binder be protected wound and anti-sealing infiltration?

Does 2) embodiment 1 binder can stop stimulate and rubescent hyperemia (feature of acute wounds and eczema madidans)?

Table 3

Number of animals in the test and age distribution

Diagnosis	Number
		Dermatitis	????13
Flegmone, abscess	????7
		Furuncle	????4
Operation	????55
		External otitis	????8
Bite (Vulnus inc., morsum)	????6

Table 4

Bacteriology's measurement result

Cultivation results	Number
		G+ and g-staphylococcus	????21
G-clostridium staphylococcus	????18
		Staphylococcus haemolyticus	????18
Proteus	????2
		Non-hemolytic g-staphylococcus	????3
The excrement staphylococcus	????1
		Klebsiella	????1
Yeast g-staphylococcus	????5
		Aseptic after 48 hours	????30

Table 5

Treat the result of clinical examination in back 3 days with embodiment 1 binder

	Have	Do not have	????％
				Color and luster	????6	????87	????7
Sensitivity	????0	????93	????0
				Abnormal smells from the patient	????1	????92	????1
Humidity	????22	????71	????24
				Pus	????5	????88	????5
Hydrophobicity	????90	????3	????97
				Viscosity	????0	????93	????0
Squama produces	????3	????90	????3

Conclusion

Use embodiment 1 binder to show that 93% case erythema disappears, and has hydrophobic effect in 97% case to little incised wound and wound.

By the result who obtains as seen, embodiment 1 binder obviously has good antibiotic property characteristic, is used for the treatment of little incised wound, postoperative wound, dermatitis and abscess.

Embodiment 5

Spray form antifungal binder is used for tinea and belongs to the athlete foot that (Tinea spp.) causes.

Most of common non-lethal skin infections are by various antibacterials and fungus, and Candida albicans causes under tinea pedis, tineacruris, tinea corporis and the skin.Miconazole is one of antifungal of common this kind of antagonism infection.Miconazole shows as and acts on cell wall and cell membrane, causes permeability changes, and has changed the ionic scintilla composition of infection cell.The product that contains miconazole (for example, the Daktarin by Janssen-Cilag) intensity of recommending is 2% powder, tincture or cream, and use 2 time in the affected part every day.

The difficulty of using antibiotic/antifungal cream, tincture or powder treatment tinea to infect is that medicine can not be attached to the affected part.If when foot (for example, athlete foot) is especially true in infection.This just causes the dissatisfied and repeated infection of therapeutic outcome.

The formula for a product of following examples has confirmed that spray form patch medicine transports the effectiveness of system, and it has improved the effect of antifungal such as miconazole greatly.Also contain chlorobutanol in the prescription, this is a kind of traditional antibacterium and antifungal, and its purposes is fully record proof in various pharmacopeia.

Spray form medicated patches long-time (about 24 hours) is attached to the skin infection surface, continues to transport active component to infecting the surface.In addition, spraying can be used for anti-fungus footwear, further infects preventing again.(for example, Daktarin) compare, product strength reduces by half (reducing to 1% from 2%), and close rate also reduces by half to only needing to use (from one day 2 times to one day 1 time) every day with other commodity.

Spray form antifungal binder is used for tinea and belongs to the athlete foot that (Tinea spp.) causes

PrescriptionMiconazole USP 1.0%w/v active component; Antimycotic anesin BP/Eur.P 0.6%w/v active component, the poly-butyl phthalate BP/Eur.P 1.0%w/v film softening agent isopropyl alcohol USP 24%w/v solvent acetone BP/Eur.P 24%w/v solvent ethyl acetate USP 40.7%w/v solvent of antibacterium/antimycotic phenol BP/Eur.P 0.2%w/v anticorrisive agent polymethylacrylic acid USNF 10.0%w/v film forming agent amounts to 100%w/v

Production method:

Miconazole and chlorobutanol are dissolved in isopropyl alcohol, phenol, the acetoneand ethyl acetate.Add poly-butyl phthalate.Gentle agitation limit, limit adds polymethylacrylic acid.The sprayer unit of packing into.

Operation instruction:

The spraying medicine effectively was attached on the skin in 24 hours.Sparge the infected zone, guarantee abundant covering.As the antimycotic liquid spray that continues to discharge, use once every day.For preventing to infect, spray in the foot every day during treating again, and weekly at least after this, continues 6 months.

25 years old women can't eradicate the fungal problems of her right crus of diaphragm in repeated multiple times and use above-mentioned spraying after many as long as five years.Before using, ulcer has taken place in regional area, sepage and pruritus.

Use miconazole/chlorobutanol spray form binder every day, continue 5 days.Her footwear spray into once a day with same product and continue 5 heaven-made anti-funguses in the footwear and handle.After 5 days, the infected zone obviously dwindles.The miconazole of stopping using is sprayed.After two weeks, (no longer sepage is not chapped, pruritus yet, and skin healing gets fine) infected and eliminated in this zone.After the first treatment, not report generation infection again during 6 months afterwards.

55 years old male also used above-mentioned spraying in lasting 5 days after the serious fungal problems of uncontrollable its right crus of diaphragm reaches more than 10.Exhausted before medicine comprises iodine tincture, Daktarin frost, unguentum acidi salicylici and Nizoral frost.

Miconazole/chlorobutanol spray form patch continued to have used 5 days once a day.His footwear spray into once a day with same product and continue 5 heaven-made anti-funguses in the footwear and handle.After 5 days, the infected zone obviously dwindles.After this skin injury place begins healing.Miconazole/chlorobutanol spraying continued again to have used 5 days, and stopped using then.Should the zone after two weeks infect and eliminate (no longer sepage, hemorrhage, chap or pruritus).After the first treatment, not report generation infection again during 6 months afterwards.All footwear continue about 6 months spray medicines weekly for 1 time and have done anti-fungus processing.

Embodiment 6

Spray form betamethasone binder is used for anaphylaxis dermatosis, eczema and psoriasis

Betamethasone is a kind of corticosteroid hormone, is used for the treatment of anaphylaxis dermatosis.The commodity of this product on market are called Betnovate ^TMCream, ointment or gel, contain the betamethasone of 0.05% to 0.1% concentration.But dosage uses as many as every day 4 times.

The practice that is widely known by the people in Australian hospital is to use Betnovate ^TMCream, gel or ointment after, available " Glad Wrap " ^TM(a kind of thin polymer film) parcel affected part by promoting absorption, extends contact time and improves the effect of medicine.

Following prescription can replace " Glad Wrap " practice effectively.Medication is also reduced to once a day for 4 times from as many as every day.Prescription also contains a kind of effective antimicrobial, with antibacterial or fungal infection under treatment and pre-seepage-proof liquid wound or the ulcer situation.

Spray form betamethasone bandage is used for the poly-butyl phthalate BP/Eur.P 1.0%w/v film softening agent isopropyl alcohol USP 24%w/v solvent acetone BP/Eur.P 24%w/v solvent ethyl acetate USP 40.7%w/v solvent of active antiinflammatory anesin BP/Eur.P 0.6%w/v active antimicrobial agent triclosan (Ciba GeigyIrgasan DP300) the 0.1%w/v anticorrisive agent polymethylacrylic acid of anaphylaxis dermatosis, eczema and psoriasis betamethasone valerate BP/Eur.P 0.12%w/v USNF 10.0%w/v film forming agent and amounts to 100%w/v

Recommended dose:

Use once in the affected part every day, is used for the treatment of eczema, psoriasis and anaphylaxis dermatosis.

Production method:

1. betamethasone is dissolved in the solvent mixture.Add triclosan and chlorobutanol.

2. gentle agitation on one side, add poly-butyl phthalate on one side, add polymethylacrylic acid then.

3. the airtight aluminium pot of packing into, and load onto switch and nozzle.

Make use-case:

A women of 23 years old suffers from serious eczema and psoriasis simultaneously from since birth, once the skin irritation of using the Betnovate frost to cause with mitigate the disease repeatedly.When pressure was arranged, her skin conditions was especially poor.Before university's examination, she has attempted using the betamethasone spray form binder of 2 weeks preparation, finds that her situation has significantly been improved.Reach the alleviation of symptom within 48 hours.Pruritus and the sepage that causes of often scratching alleviated quickly and effectively.She only needs to use spraying once every night, and needn't use sooner or later.She can be with betamethasone spray form binder to have a shower, and medication again.The affected part is healed finely, particularly can not put binder in the above to prevent the position in medicated clothing scratch affected part.

Embodiment 7

A kind of first-selected auxiliary treatment of spray form pyrilamine antihistaminic adhesive patch-burn, scald, sting is to use as antipruritic and local anesthetic in the patient's condition of feature with violent pruritus or pain at all.

Pyrilamine is to be widely known by the people, through fully testing and widely used antihistaminic.Surpass 100 kinds of medicines and contain pyrilamine as one of its main component.

The poly-butyl phthalate BP/Eur.P 1.0%w/v film softening agent isopropyl alcohol USP 24%w/v solvent acetone BP/Eur.P 24%w/v solvent ethyl acetate USP 40.7%w/v solvent of active antihistamine anesin BP/Eur.P 0.6%w/v active antimicrobial agent triclosan (Ciba Geigy Irgasan DP300) the 0.1%w/v anticorrisive agent polymethylacrylic acid USNF of spray form mepyramine antihistamine adhesive patch mepyramine maleate BP/Eur.P 2.0%w/v 10.0%w/v film forming agent amounts to 100%w/v

Production method:

1. mepyramine maleate is dissolved in the solvent mixture.Add triclosan and chlorobutanol.

2. gentle agitation on one side, add poly-butyl phthalate on one side, add polymethylacrylic acid then.

3. the airtight aluminium pot of packing into, and load onto switch and nozzle.

One group of boy of boy scout and father and mother thereof have used spray form pyrilamine antihistaminic adhesive patch during nearest camping.Total observation shows that this prescription alleviates the symptom of sting quickly and effectively among the adult.Once, boy of 12 years old bonfire moderate the back of the hand of having burnt of when roasting fruit juice jelly, being encamped.After the medication once, pain is alleviated rapidly, does not blister.Show that pyrilamine antihistaminic spray form binder also forms the covering of protectiveness on wound, and be waterproof.Even binder is still stayed on the skin depolymerization voluntarily after about 24 hours after swimming.

Embodiment 8

Other compositionss are prepared as follows:

(A) chlorhexidine acetate 0.5%w/w

The 0.07%w/w triclosan

The 0.6%w/w chlorobutanol

The 10%w/w polymethylacrylic acid

1.2%w/w gathers butyl phthalate

The 4%w/w isopropyl alcohol

24%w/w acetone

Ethyl acetate adds to 100%w/w

(B) phenoxyethanol 2%w/w

The 0.07%w/w triclosan

The 0.6%w/w chlorobutanol

The 10%w/w polymethylacrylic acid

1.2%w/w gathers butyl phthalate

The 4%w/w isopropyl alcohol

24%w/w acetone

Ethyl acetate adds to 100%w/w

(C) phenethanol 2%w/w

The 0.07%w/w triclosan

The 0.6%w/w chlorobutanol

The 10%w/w polymethylacrylic acid

1.2%w/w gathers butyl phthalate

The 4%w/w isopropyl alcohol

24%w/w acetone

Ethyl acetate adds to 100%w/w

Claims (23)

1. non-aerosol spray shape skin patch composition, it comprises:

(a) at least a water-insoluble basically film former;

(b) at least a film plasticizer;

(c) at least a water soluble compound; With

(d) at least a organic solvent;

When being sprayed onto on the skin and after drying, compositions forms a softness, the porous compatible skin patch of physiology simultaneously.

2. according to the compositions of claim 1, wherein at least a water soluble compound comprises at least a physiologically active ingredient.

3. according to the compositions of claim 2, wherein at least a physiologically active ingredient is a kind of antibacterial and/or antifungal.

4. according to the compositions of claim 3, wherein antibacterial is a kind of quaternary ammonium compound.

5. according to the compositions of claim 4, wherein quaternary ammonium compound is selected from Cetrimide, alkylaryl tri alkyl ammomium chloride, alkylaryl trimethyl ammonium chloride, bromine diamantane (obsolete) ammonium, benzalkonium chloride, benzethonium chloride, bromobenzyl moon first ammonium, cetalkonium chloride, cethexonium bromide, hexadecyltrimethylammonium chloride and cetyldimethylethylambromide bromide ammonium.

6. according to the compositions of claim 5, wherein quaternary ammonium compound is a Cetrimide.

7. according to the compositions of claim 3, it comprises a kind of water-soluble antimicrobial and a kind of water solublity antifungal.

8. the chemical compound arbitrary according to claim 7, wherein antibacterial is a kind of quaternary ammonium compound, and antifungal is selected from chlorobutanol, phenol, phenol derivatives, salicylic acid, the trivial suffering of bifurcation pyridine, amorolfine, amphotericin, azole derivatives and related compound, benzoyl disulphide, bromine chlorine water poplar anilide, buclosamide, Butenafine, sad candicidin, Chlorphenesin, ciclopirox olamine, cilofungin, D25, flucytosine, griseofulvin, hachimycin, siccolam, hamycin, amidine at the bottom of the isethionic acid hydroxyl, loflucarban, mepartricin, pimaricin, furfural oxime, paranitrophenol, nystatin, pentamycin, propanoic acid, protiofate, pyrrolnitrin, Sulbentine, terbinafine, tolciclate, tineatonsurans is moved back, triacetin and undecylenic acid.

9. chemical compound according to Claim 8, wherein antifungal is a chlorobutanol.

10. according to any one compositions in the claim 1 to 9, comprise at least a physiologically active ingredient in addition.

11. compositions according to claim 10, wherein at least a physiologically active ingredient is selected from antifungal agent, antimicrobial drug, antiseptic, antiparasitic, nicotine, corticosteroid, analgesic, coronary dilation agent, cardiac tonic, antihistaminic, anti-inflammatory agent, anticoagulant medicine, growth hormone, gonadal hormone, or the medicine commonly used of following systemic disease: digestive system, central nervous system, musculoskeletal system, urogenital system, allergy and immune system, respiratory system, or biologically active peptide or biological activity protein.

12. according to the compositions of claim 11, wherein at least a physiologically active ingredient is a triclosan.

13. according to the compositions of claim 1, wherein film former is selected from polymethylacrylic acid, polybutyl methacrylate and polyacrylic acid.

14. according to the compositions of claim 1, wherein film plasticizer is poly-butyl phthalate.

15. according to the compositions of claim 1, wherein organic solvent is selected from isopropyl alcohol, acetoneand ethyl acetate.

16. a spray form patch dermal drug transports compositions, provides

(a) at least a water-insoluble basically film former;

(b) at least a film plasticizer;

(c) at least a water soluble compound;

(d) at least a organic solvent; With

(e) one or more physiologically active ingredients or a kind of its prodrug;

When being sprayed onto on the skin and after drying, compositions forms a softness, the porous compatible skin patch of physiology simultaneously, in disintegrate or depolymerization in a period of time on the skin, provides transdermal drug to transport.

17. compositions according to claim 16, wherein physiologically active ingredient is selected from antifungal agent, antimicrobial drug, antiparasitic, nicotine, corticosteroid, analgesic, coronary dilation agent, cardiac tonic, antihistaminic, anti-inflammatory agent, anticoagulant medicine, growth hormone, gonadal hormone, or the medicine commonly used of following systemic disease: digestive system, central nervous system, musculoskeletal system, urogenital system, allergy and immune system, respiratory system, or biologically active peptide or biological activity protein.

18. a non-aerosol spray shape skin patch composition, it comprises:

0.01% to 10%w/w one or more water-fast chemical compounds

0.01% to 10%w/w one or more physiologically active ingredients

1% to 5%w/w polymethylacrylic acid

0.1% to 20%w/w poly-butyl phthalate

0% to 90%w/w isopropyl alcohol

0% to 90%w/w acetone

Ethyl acetate adds to 100%w/w,

When being sprayed onto on the skin and after drying, compositions forms a softness, the porous compatible skin patch of physiology simultaneously.

19. according to the compositions of claim 18, it comprises:

0.05%w/w bromine alkanamine

The 0.07%w/w triclosan

The 0.6%w/w chlorobutanol

The 10%w/w polymethylacrylic acid

1.2%w/w gathers butyl phthalate

The 4%w/w isopropyl alcohol

24%w/w acetone

Ethyl acetate adds to 100%w/w

20. a method that promotes wound healing or need the patient physiological active component of this treatment, the method comprise to patient's wound or dermal administration effective dose according to any one compositions in the claim 1 to 19

21. the method for the following disease of treatment: skin wound, fungal infection, eczema, in skin with skin on and/or bacterial infection, athlete foot, the skin ulcer relevant with skin wound, burn, scald, sting, anaphylactic disease, psoriasis, pruritus and pain, it comprises to dermal administration according to any one compositions in the claim 1 to 19.

22. the spray form skin patch composition as any one definition in the claim 1 to 19 is used for the purposes that promotes wound healing or give the patient physiological active ingredient medicine in production.

23. the spray form skin patch composition as any one definition in the claim 1 to 19 is used for the treatment of skin wound, fungal infection, bacterial infection, athlete foot, skin ulcer in production, burns, the purposes in the medicine of scald, sting, pruritus or pain.